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A New Cholesterol Transporter

Potential mechanisms of cholesterol transfer from NPC2 to membranes.

Niemann-Pick type C disease is a lipid storage disorder characterized by the accumulation of unesterified cholesterol and glycolipids in the endosomal/lysosomal system. The disease is caused by defects in either of two genes that code for the proteins NPC1 and NPC2. Although there is abundant indirect evidence that suggests a role for the NPC proteins in late endosomal/lysosomal transport of cholesterol, their precise functions at the cellular and molecular levels have not yet been determined.

NPC2 is a small intralysosomal protein that has been characterized biochemically as a cholesterol-binding protein. Using a fluorescence dequenching assay, Sunita R. Cheruku and colleagues monitored the kinetics of cholesterol transfer from NPC2 to model phospholipid membranes. They showed that transfer of cholesterol from NPC2 likely involves a collisional mechanism and is optimal in an acidic environment such as the endosomal/lysosomal compartment. They further demonstrated that NPC2 dramatically increases the rate of transfer of lyso-bisphosphatidic acid-containing vesicles. These studies support a role for the NPC2 protein in the transport of low density lipoprotein-derived cholesterol out of the endosomal/lysosomal compartment.

FOOTNOTES

See referenced article, J. Biol. Chem. 2006, 281, 31594-31604

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